Hydrochloric Acid → HCID 53846384, Verbindung

HRID 1378617Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1378617
[F:1][C:2]([F:7])([F:6])[C:3]([NH2:5])=O.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=S.Br[CH:23]([C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)[C:24]([C:26]1[CH:31]=[CH:30][C:29]([S:32][CH3:33])=[CH:28][CH:27]=1)=O.Cl.[OH-].[Na+].[S:44]1C=CN=C1>C1(C)C=CC=CC=1.C(Cl)Cl>[F:40][C:37]1[CH:38]=[CH:39][C:34]([C:23]2[S:44][C:3]([C:2]([F:7])([F:6])[F:1])=[N:5][C:24]=2[C:26]2[CH:31]=[CH:30][C:29]([S:32][CH3:33])=[CH:28][CH:27]=2)=[CH:35][CH:36]=1

Komponenten

9

Edukt 6

HCID 313Hydrochloric AcidHCID 9256ThiazoleHCID 14798Sodium HydroxideHCID 14817Phosphorus sulfide (P2S5)HCID 67717TrifluoroacetamideHCID 54373829HCID 54373829, Verbindung

Produkt 1

HCID 53846384HCID 53846384, VerbindungAusbeute 23 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittel2×HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of trifluoroacetamide (13.7 g, 121.2 mmol) in toluene (30 mL) was added solid P4S10 (5.4 g, 12.1 mmol) and the mixture refluxed for 60 hours. The resulting orange "coarse" suspension was cooled to room temperature and the solid pulverized to form a fine suspension. One fourth of this toluene suspension (7.5 mL, ca. 30 mmol of theory) was transferred to a 25 mL round bottom flask and 2-bromo-2-(4-fluorophenyl)-1-(4-methylthiophenyl)ethanone (1.24 g, 3.66 mmol) (Example 20, Step 2) added in one portion. This suspension was heated to reflux for 1.5 hours, cooled to 50° C., and 1.0 N HCl solution (1 mL) added carefully and reflux continued for 1 hour more. This reaction was cooled to room temperature and let stand overnight. To this solution was added 2 N NaOH solution until the exotherm subsided and the reaction was stirred for 1 hour longer. The resulting black suspension was diluted with methylene chloride and washed with NaHCO3 saturated solution, dried over Na2SO4, filtered and concentrated in vacuo yielding a brown semi-solid. This crude thiazole was flash chromatographed (9:1 hexane:methylene chloride) yielding 5-(4-fluorophenyl)-4-(4-methylthiophenyl)-2-trifluoromethylthiazole (0.28 g, 23%) as yellow oil which slowly solidified mp: 59°-60° C.; 1HNMR (CDCl3) 300 mHz 7.43 (d, J=8.48, 2 H), 7.40-7.32 (m, 2 H), 7.17 (d, J=8.48 Hz, 2 H), 7.08 (t, J=8.48, 2 H) 2.46 (s, 3 H); MS (EI) m/z 369 (M+H). HRMS Δ=-3.17 mmu.

Aufarbeitung

  1. temperaturethe mixture refluxed for 60 hours
  2. customto form a fine suspension
  3. temperatureThis suspension was heated
  4. temperatureto reflux for 1.5 hours
  5. temperaturecooled to 50° C.
  6. temperaturereflux
  7. temperatureThis reaction was cooled to room temperature
  8. waitlet stand overnight
  9. washwashed with NaHCO3 saturated solution
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customyielding a brown semi-solid
  14. customchromatographed (9:1 hexane:methylene chloride)

Quellen und Nachweise

ORD-Eintrag
ord-364d8840647a46f99c6cb2defab9ba5c
Quelldatensatz
uspto-grants-1997_09
Patentnummer
US05668161

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